Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related death in the U.S. HCC disproportionally affects racial/ethnic minority and socioeconomically disadvantaged populations, with higher age-adjusted mortality observed in non-Hispanic blacks and Hispanic whites than non-Hispanic whites. To evaluate these disparities, we will use an adapted Warnecke/Centers for Population Health and Health Disparities ecological multi-level model attributing disparate health outcomes to biological-environmental interactions between and across distal (population social conditions and policies), intermediate (social and physical contexts including social relationships), and proximal (individual demographics and biological responses) determinants. Applying this model to HCC disparities will facilitate identification of key drivers of disparities in prognosis, which is the first necessary step to develop intervention strategies aimed at improving survival and reducing disparities following HCC diagnosis. Specifically, our proposal will characterize the contribution of proximal, intermediate, and distal determinants to disparities in 3 known measures of HCC prognosis: a) tumor stage at diagnosis, b) receipt of timely and guideline-concordant HCC treatment, and c) overall survival. Leveraging existing clinical databases and a biorepository of stored serum, we will conduct a multi-center study using electronic medical record-derived, patient-reported, provider-reported, and serum- based biological factors in a cohort of ~5000 patients newly diagnosed with HCC over a 13-year period to: Aim 1: Characterize the contribution of proximal, intermediate, and distal determinants of racial/ethnic and socioeconomic disparities in HCC tumor stage at diagnosis Aim 2: Determine racial/ethnic and socioeconomic disparities in receipt of timely and guideline- concordant HCC treatment including proximal, intermediate, and distal determinants Aim 3: Identify proximal, intermediate, and distal determinants of racial/ethnic and socioeconomic disparities in overall survival following HCC diagnosis Overall, we will identify factors across and within multiple levels associated with disparities in HCC prognosis between non-Hispanic white, Hispanic white, and non-Hispanic black patients as well as low versus high SES class in a large, racial/ethnically and socioeconomically diverse diverse cohort of ~5000 HCC patients. Our study will provide an understanding of why HCC prognosis disparities exist and at what level interventions should be implemented to reduce disparities improving overall survival.